scholarly journals Disease-Modifying Potential of Metformin and Alendronate in an Experimental Mouse Model of Osteoarthritis

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1017
Author(s):  
Lyudmila Belenska-Todorova ◽  
Sevdalina Nikolova Lambova ◽  
Stela Stoyanova ◽  
Elenka Georgieva ◽  
Tsvetelina Batsalova ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Ex Vivo ◽  
Histopathological Examination ◽  
Marrow Cell ◽  
Chronic Phase ◽  
Serum Levels ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Control Group

Osteoarthritis (OA) is the most common degenerative joint disease causing progressive damages of the cartilage and subchondral bone, synovial inflammation, and severe pain. Despite the complex pathomorphological changes that occur in OA, the approach to different forms of OA is standardized. The global results from pharmacological treatment are not satisfactory. Hence, this study aimed to explore the effects of metformin, alendronate, and their combination on OA development and progression in mice with collagenase-induced osteoarthritis (CIOA). Female ICR (CD-2) mice were randomized to five groups: control group, CIOA untreated, CIOA + metformin, CIOA + alendronate, and CIOA + metformin + alendronate. OA was induced by the intra-articular (i.a.) injection of collagenase. OA phenotype was analyzed by flow cytometry (bone marrow cell differentiation), ELISA (serum levels of the adipokines leptin and resistin), and histology (pathological changes of the knee joint). Treatment with metformin, alendronate, or their combination inhibited the expression of RANK and RANKL on osteoblasts and osteoclasts obtained by ex vivo cultivation of bone marrow cells in mineralization or osteoclastogenic media. In addition, metformin treatment was effective for the attenuation of fibroblast differentiation, but not of mesenchymal stem cells (MSCs), while alendronate had an opposite effect. The combination of metformin and alendronate had a suppressive effect on both MSCs and fibroblasts differentiation. Treatment with metformin, alendronate, and their combination decreased serum concentrations of leptin and resistin in the chronic phase of arthritis. The histopathological examination showed that compared with the untreated CIOA group (OA score 9), the groups treated with metformin (OA score 4) or alendronate (OA score 6) had lower scores for cartilage changes. Metformin combined with alendronate significantly decreased the degree of cartilage degeneration (OA score 2), suggesting that this combination might be a useful approach for the treatment of OA patients.

scholarly journals Differential induction of apoptosis in lymphoid tissues during sepsis: variation in onset, frequency, and the nature of the mediators

Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4261-4275 ◽  
Author(s):  
A Ayala ◽  
CD Herdon ◽  
DL Lehman ◽  
CA Ayala ◽  
IH Chaudry
Keyword(s):  
Bone Marrow ◽  
Immune Cell ◽  
Bone Marrow Cells ◽  
Ex Vivo ◽  
Marrow Cell ◽  
Cecal Ligation ◽  
Polymicrobial Sepsis ◽  
Cell Populations ◽  
Lymphoid Tissues ◽  
Marrow Cells

Apoptosis (Ao), is a process by which cells undergo a form of nonnecrotic cellular suicide. Although for most cells this is a constitutive process, it can be induced in immature and differentiating immune cell populations by stress mediators associated with inflammation. This inducible form of A(o) is referred to as programmed cell death. However, it is not clear whether hematopoietic cell populations such as the thymus and bone marrow are induced to undergo A(o) during polymicrobial sepsis. To assess this, thymocytes, bone marrow cells, or splenocytes (as a source of comparative nonhematopoietic cells) were harvested from C3H/HeN mice at 1, 4, or 24 hours after cecal ligation and puncture (CLP; to induce polymicrobial sepsis) or sham-CLP (Sham). The results showed that mixed bone marrow cells ex vivo, although not to the same extent as thymus, showed a marked increase in the percentage of cells in A(o), increased endonuclease activity, and a significant decrease in cell yield at 24 hours but not at 4 hours after CLP. Similar changes were not evident in splenocytes. Phenotypic, as well as morphologic assessment, indicated that most of the increase in apoptotic cells in the thymus was associated with the immature T cells (CD4+CD8+) and CD8-CD4- cells. In contrast, the increase in bone marrow cell A(o) was associated with only the B220+ cells, with no significant contribution from myeloid cells. Treatment of CLP mice in vivo with either RU-38486 or PEG-(rsTNF- R1)2 was unable to reverse the increased A(o) in the bone marrow of these animals. Taken together, these findings indicate that A(o) as a process induced by polymicrobial sepsis is not limited to the thymus, but can also be detected in the bone marrow. However, unlike thymic A(o), bone marrow is not affected directly/indirectly by glucocorticoids or tumor necrosis factor released during sepsis.

scholarly journals Treatment with at Homeopathic Complex Medication Modulates Mononuclear Bone Marrow Cell Differentiation

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Beatriz Cesar ◽  
Ana Paula R. Abud ◽  
Carolina C. de Oliveira ◽  
Francolino Cardoso ◽  
Raffaello Popa Di Bernardi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Differentiation ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Ex Vivo ◽  
Marrow Cell ◽  
Macrophage Colony ◽  
Total Bone Marrow

A homeopathic complex medication (HCM), with immunomodulatory properties, is recommended for patients with depressed immune systems. Previous studies demonstrated that the medication induces an increase in leukocyte number. The bone marrow microenvironment is composed of growth factors, stromal cells, an extracellular matrix and progenitor cells that differentiate into mature blood cells. Mice were our biological model used in this research. We now reportin vivoimmunophenotyping of total bone marrow cells andex vivoeffects of the medication on mononuclear cell differentiation at different times. Cells were examined by light microscopy and cytokine levels were measuredin vitro. Afterin vivotreatment with HCM, a pool of cells from the new marrow microenvironment was analyzed by flow cytometry to detect any trend in cell alteration. The results showed decreases, mainly, in CD11b and TER-119 markers compared with controls. Mononuclear cells were used to analyze the effects ofex vivoHCM treatment and the number of cells showing ring nuclei, niche cells and activated macrophages increased in culture, even in the absence of macrophage colony-stimulating factor. Cytokines favoring stromal cell survival and differentiation in culture were inducedin vitro. Thus, we observe that HCM is immunomodulatory, either alone or in association with other products.

scholarly journals Omega3 Fatty Acids Intake Versus Diclofenac in Osteoarthritis Induced in Experimental rats

2017 ◽  
Vol 7 (4) ◽  
pp. 291 ◽  
Author(s):  
Mohammed M. El-Seweidy ◽  
Sousou I. Ali ◽  
Sahar E. Elsweify ◽  
Abdelmoneim A. Ali ◽  
Mai M. Mashhour
Keyword(s):  
Fatty Acids ◽  
Serum Levels ◽  
Interleukin 10 ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Control Group ◽  
Omega 3 ◽  
Anti Inflammatory ◽  
Histopathological Results ◽  
Remodeling Pattern

Background: Osteoarthritis (OA) is a degenerative joint disease, characterized by abnormal remodeling pattern of joints driven by inflammatory mediators within the affected joints. Its symptoms are many like pain, stiffness, and decreased function.Objective:  The present study mainly focused on the anti-inflammatory effect of omega 3 fatty acids (F.As) versus diclofenac, non-steroidal anti-inflammatory drug in OA induced in ratsDesign: Intraarticular injection of monosodiumiodoacetate (MIA) 24.6 mg/kg in 0.6 ml saline was used to induce OA. Diclofenacand omega-3 F. These were administered orally, daily for 21 days and after 24 hours of OA induction.Results: Osteoarthritis induction resulted in an increase in serum levels of IL-6 (479.5%), TNF-a(545.5%), and CRP (754.2%) along with IL-10 level decrease (70.3%) as compared to normal group. Diclofenac intake demonstrated significant increase of IL-6 (24.9%), CRP (88.6%), and TNF-a (25.2%) compared to the OA control group. Omega 3 FAs intake showed significant reduction in inflammatory markers along with IL-10 increase, in comparison to OA group. Both treatment demonstrated a significant increase in TIMP2 along with decreased MMP2 and MPO in comparison with OA control. Positive correlation of IL-6 with MPO (r = 0.7, P=0.002), and negative one with IL-10 (r = 0.9, p<0.0001) and TIMP2 (r = -0.5, p<0.008) was observed. Interleukin-10 was negatively correlated with MMP2 (r = - 0.5, p<0.007) and MPO (r = -0.8, p<0.0001).Conclusion: Data derived from biochemical and histopathological results, indicated that omega3 FAs may be expressed as a natural anti-inflammatory agent of a significant potential in OA with evident remarkable effect.Keywords: OA; omega3FAs; diclofenac; MMP2; TIMP2; MPO

scholarly journals Establishment of an Ex Vivo Inflammatory Osteoarthritis Model With Human Osteochondral Explants

2021 ◽  
Vol 9 ◽  
Author(s):  
Kaihu Li ◽  
Penghui Zhang ◽  
Yong Zhu ◽  
Mauro Alini ◽  
Sibylle Grad ◽  
...  
Keyword(s):  
Femoral Head ◽  
Matrix Metalloproteinase ◽  
Ex Vivo ◽  
Degenerative Joint Disease ◽  
New Drugs ◽  
Joint Disease ◽  
Control Group ◽  
Pathophysiological Mechanism ◽  
Superficial Zone ◽  
Matrix Metalloproteinase 1

Osteoarthritis (OA) is the most common degenerative joint disease without clear pathophysiological mechanism and effective drugs for treatment. Although various animal models exist, the translation of the outcome into clinics remains difficult due to species differences. In this study, an ex vivo inflammatory OA model was induced using different concentrations of interleukin one beta (IL-1β) and tumor necrosis factor α (TNF-α) on explants from the human femoral head. In the inflammatory OA groups, the gene expression levels of cartilage catabolism (matrix metalloproteinase 1 (MMP1), matrix metalloproteinase 3 (MMP3)), and inflammation (interleukin 6 (IL-6), interleukin 8 (IL-8)) markers were significantly upregulated, while the anabolic genes (collagen 2 (COL2), aggrecan (ACAN), and proteoglycan 4 (PRG4)) were downregulated compared to the control group. The release of cytokines (IL-6, IL-8) and nitric oxide (NO) in the conditioned medium was also upregulated in inflammatory OA groups. The Safranin O/Fast Green staining showed loss of proteoglycan in the superficial zone cartilage after cytokine treatment. The results indicated that an ex vivo inflammation and degeneration model was successfully established using osteochondral explants from the human femoral head. This model can be used to elucidate the in-depth mechanism of inflammatory OA and to screen new drugs for OA treatment.

Withdrawn: Hepatoprotective effects of Tribulus terrestris L. (Zygophyllales: Zygophyllaceae) hydro-alcholic extract on non-alcoholic fatty liver-induced rats

2016 ◽  
Vol 3 (5) ◽  
pp. 143
Author(s):  
Fatemeh Almasi ◽  
Mozafar Khazaei ◽  
Shima Chehrei ◽  
Ali Ghanbari
Keyword(s):  
Fatty Liver ◽  
Liver Tissue ◽  
Serum Lipid ◽  
Histopathological Examination ◽  
Serum Levels ◽  
Lipid Profiles ◽  
Control Group ◽  
Tribulus Terrestris ◽  
Protective Effects ◽  
Alcoholic Fatty Liver

Non-alcoholic fatty liver induces many complications to the liver tissue and also serum related parameters. Medicinal plants are the safe therapeutic strategy for the treatment of diseases. In this regards, the present study was conducted to evaluate the effect of Tribulus terrestris L. (Zygophyllales: Zygophyllaceae) extract on non-alcoholic fatty liver in rats. In this experimental study, thirty male Wistar rats were divided into five groups (n = 6). Animals in experimental groups were received high fructose diet (70%) (HDF) daily alone or in combined with daily intraperitoneal injection of 500, 700 and 1,000 mg/kg extract of T. terrestris. Control group of rats was feed with standard chow. The serum levels of biomarkers of liver and serum lipid profiles were assessed, also histopathological examination of liver tissue done. Data were analyzed using One-way ANOVA method followed by Tukey’s post-hoc multiple comparison test and P < 0.05 was considered statistically significant. There were significant improvements for biomarkers of liver tissue (P < 0.05) and serum lipid profiles (P < 0.01) in the HFD-fed rats that were treated with T. terrestris extract compare to HFD-fed group. In addition, accumulation of lipids in hepatocytes was significantly reduced in the HFD-fed + extract administrated groups in comparison to HFD-fed rats (P < 0.01). T. terrestris extract has protective effects against non-alcoholic fatty liver by changing biomarkers of liver tissue, serum lipid profiles and histopathological anomalies of liver tissue, to normal range.

Evaluation of genotoxicity of pan masala employing chromosomal aberration and micronucleus assay in bone marrow cells of the mice

2009 ◽  
Vol 25 (7) ◽  
pp. 467-471 ◽  
Author(s):  
BN Mojidra ◽  
K. Archana ◽  
AK Gautam ◽  
Y. Verma ◽  
BC Lakkad ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chromosome Aberration ◽  
Chromosomal Aberration ◽  
Bone Marrow Cells ◽  
Micronucleus Assay ◽  
Control Group ◽  
Genotoxic Potential ◽  
Polychromatic Erythrocytes ◽  
Significant Difference ◽  
Marrow Cells

Pan masala is commonly consumed in south-east Asian and other oriental countries as an alternate of tobacco chewing and smoking. Genotoxic potential of pan masala (pan masala plain and pan masala with tobacco known as gutkha) was evaluated employing chromosome aberration (CA) and micronucleus (MN) assay in vivo. Animals were exposed to three different doses (0.5%, 1.5% and 3%) of pan masala plain (PMP) and gutkha (PMT) through feed for a period of 6 months and micronucleus and chromosomal aberrations were studied in the bone marrow cells. Induction of mean micronuclei in polychromatic erythrocytes (MNPCE) and normochromatic erythrocyte (MNNCE) was higher in both types of pan masala treated groups with respect to control group. Both pan masala plain and gutkha treatment significantly induced the frequency of MNPCE and MNNCE in the bone marrow cells, indicating the genotoxic potential. Furthermore, slight decline in the ratio of polychromatic erythrocytes to normochromatic erythrocytes was also noticed, suggesting the cytotoxic potential even though the ratio was statistically non significant. A dose-dependent, significant increase in chromosome aberration was observed in both types of pan masala treated mice with respect to control. However, no significant difference in micronucleus and chromosomal aberration induction was noticed between two types of pan masala exposed (PMP and PMT) groups. Results suggest that both types of pan masala, i.e. plain and gutkha, have genotoxic potential.

130 Burn Injury Reduces Bone Marrow Mesenchymal Stem Cells and Sensitizes Their Adrenergic Receptor Subgroups in a Murine Model

2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S87-S88
Author(s):  
Kuzhali Muthumalaiappan ◽  
Maria Camargo Johnson ◽  
Julia Walczak ◽  
Vimal Subramaniam ◽  
Anthony J Baldea ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adrenergic Receptor ◽  
Burn Injury ◽  
Bone Marrow Cells ◽  
Ex Vivo ◽  
Traumatic Injury ◽  
Hematopoietic Cell ◽  
The Right

Abstract Introduction Previous burn and traumatic injury studies have established that adrenergic signaling is increased after burn injury and may lead to an impairment of hematopoietic cell development in the bone marrow (BM). Nonetheless, mesenchymal stem cells (MSCs), which have gained momentum in regenerative medicine also play a predominant role in the BM niche. Understanding the propensity of the adrenergic receptor (AR) response by MSCs can be utilized for devising targeted therapies. However, the traditional plastic adherence procedure using ex vivo culture of BM cells for several weeks may skew the actual characteristics of MSCs. Our current study focused on isolating MSCs from freshly obtained BM in a murine scald burn model with a goal to characterize the expression pattern of native AR subgroups present on BM MSCs as compared to sham mice. Methods Eight, two-month-old adult female mice were subjected to a 15% total body 3rd degree burn or sham burn. The mice were sacrificed 7 days later. Femurs were removed and total bone marrow cells were flushed out. Multi parametric flow cytometry was used to gate for cells negative for hematopoietic cell markers (CD45, CD11B) and positive for MSC markers (CD105, CD106, SSEA, Ly6A) and AR subgroups (α1, α2, β1, β2, β3). We measured the number of BM MSCs, quantified the subtypes of ARs present on MSCs, and compared the ratio of AR antibody binding per total MSC population. Results Overall the frequency of MSCs per million total BM cells decreased by 48% post-burn injury with165,300 ± 194 in sham versus 110,000 ± 30 in burn displayed as bar graph in Panel A. Over 90% of MSCs consistently express β2 AR and only 10% express α2 AR subgroup in both scald and sham burn. Presence of other subgroups ranged from 50% to 80% of MSCs as seen in histograms to the right of dotted line in Panel B. Our AR propensity score based on AR mean fluorescence intensity adjusted to total number of MSCs present was increased by 2.8-fold for α1, 2.5-fold for β1, 1.6-fold for β3, and 1.3-fold for β2 AR subgroups (Panel C). These findings indicate burn injury not only decreases the frequency of BM MSCs but also increases the affinity of certain AR subgroups present on MSCs. Since BM MSCs are the major source of cytokines, chemokines and growth factors; detailed studies on AR mediated signaling in BM MSCs is warranted. Conclusions Polarization of AR signaling in BM MSCs by burn-induced catecholamines may have broader implications for comorbidities such as bone resorption and muscle wasting observed in human patients post burn trauma.

scholarly journals CD34+ human marrow cells that express low levels of Kit protein are enriched for long-term marrow-engrafting cells

Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4136-4142 ◽  
Author(s):  
I Kawashima ◽  
ED Zanjani ◽  
G Almaida-Porada ◽  
AW Flake ◽  
H Zeng ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
In Utero ◽  
Fetal Sheep ◽  
Hematopoietic Stem ◽  
Show Evidence ◽  
Marrow Cells

Using in utero transplantation into fetal sheep, we examined the capability of human bone marrow CD34+ cells fractionated based on Kit protein expression to provide long-term in vivo engraftment. Twelve hundred to 5,000 CD34+ Kit-, CD34+ Kit(low), and CD34+ Kit(high) cells were injected into a total of 14 preimmune fetal sheep recipients using the amniotic bubble technique. Six fetuses were killed in utero 1.5 months after bone marrow cell transplantation. Two fetuses receiving CD34+ Kit(low) cells showed signs of engraftment according to analysis of CD45+ cells in their bone marrow cells and karyotype studies of the colonies grown in methylcellulose culture. In contrast, two fetuses receiving CD34+ Kit(high) cells and two fetuses receiving CD34+ Kit- cells failed to show evidence of significant engraftment. Two fetuses were absorbed. A total of six fetuses receiving different cell populations were allowed to proceed to term, and the newborn sheep were serially examined for the presence of chimerism. Again, only the two sheep receiving CD34+ Kit(low) cells exhibited signs of engraftment upon serial examination. Earlier in studies of murine hematopoiesis, we have shown stage-specific changes in Kit expression by the progenitors. The studies of human cells reported here are in agreement with observations in mice, and indicate that human hematopoietic stem cells are enriched in the Kit(low) population.

scholarly journals GPR109A mediates the effects of hippuric acid on regulating osteoclastogenesis and bone resorption in mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jin-Ran Chen ◽  
Haijun Zhao ◽  
Umesh D. Wankhade ◽  
Sree V. Chintapalli ◽  
Can Li ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Resorption ◽  
Bone Mass ◽  
Hippuric Acid ◽  
Ex Vivo ◽  
Marrow Cell ◽  
Osteoclast Differentiation ◽  
Bone Homeostasis ◽  
Wild Type ◽  
Osteoclast Precursors

AbstractThe G protein-coupled receptor 109 A (GPR109A) is robustly expressed in osteoclastic precursor macrophages. Previous studies suggested that GPR109A mediates effects of diet-derived phenolic acids such as hippuric acid (HA) and 3-(3-hydroxyphenyl) propionic acid (3-3-PPA) on promoting bone formation. However, the role of GPR109A in metabolic bone homeostasis and osteoclast differentiation has not been investigated. Using densitometric, bone histologic and molecular signaling analytic methods, we uncovered that bone mass and strength were significantly higher in tibia and spine of standard rodent diet weaned 4-week-old and 6-month-old GPR109A gene deletion (GPR109A−/−) mice, compared to their wild type controls. Osteoclast numbers in bone and in ex vivo bone marrow cell cultures were significantly decreased in GPR109A−/− mice compared to wild type controls. In accordance with these data, CTX-1 in bone marrow plasma and gene expression of bone resorption markers (TNFα, TRAP, Cathepsin K) were significantly decreased in GPR109A−/− mice, while on the other hand, P1NP was increased in serum from both male and female GPR109A−/− mice compared to their respective controls. GPR109A deletion led to suppressed Wnt/β-catenin signaling in osteoclast precursors to inhibit osteoclast differentiation and activity. Indeed, HA and 3-3-PPA substantially inhibited RANKL-induced GPR109A expression and Wnt/β-catenin signaling in osteoclast precursors and osteoclast differentiation. Resultantly, HA significantly inhibited bone resorption and increased bone mass in wild type mice, but had no additional effects on bone in GPR109A−/− mice compared with their respective untreated control mice. These results suggest an important role for GPR109A during osteoclast differentiation and bone resorption mediating effects of HA and 3-3-PPA on inhibiting bone resorption during skeletal development.

scholarly journals Association of the translocation (15;17) with malignant proliferation of promyelocytes in acute leukemia and chronic myelogenous leukemia at blastic crisis

Blood ◽  
1986 ◽  
Vol 67 (2) ◽  
pp. 270-274 ◽  
Author(s):  
S Misawa ◽  
E Lee ◽  
CA Schiffer ◽  
Z Liu ◽  
JR Testa
Keyword(s):  
Bone Marrow ◽  
Chronic Myelogenous Leukemia ◽  
Bone Marrow Cells ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Blastic Crisis ◽  
Cytogenetic Studies ◽  
Chromosomal Breakpoints ◽  
Variant Translocation ◽  
Marrow Cells

Abstract Cytogenetic studies were performed on nine patients with acute promyelocytic leukemia. Every patient had an identical translocation (15;17) or, in one case, a variant three-way rearrangement between chromosomes 7, 15, and 17. Another patient with chronic myelogenous leukemia was examined at the time of blastic crisis when the patient's bone marrow was infiltrated by hypergranular promyelocytes and blasts. Bone marrow cells contained a t(15;17) as well as a Ph1 chromosome. Only the latter abnormality was observed in the chronic phase of the disease. The translocation (15;17) was detected in all ten patients when bone marrow or peripheral blood cells were cultured for 24 hours prior to making chromosome preparations. However, the t(15;17) was not seen in three of these same cases when bone marrow cells were processed directly. These findings indicate that the t(15;17) is closely associated with acute proliferation of leukemic promyelocytes and that detection of this karyotypic defect may be influenced by the particular cytogenetic processing method used in different laboratories. An analysis of the banding pattern in the variant translocation provided additional evidence favoring chromosomal breakpoints at or very near the junction between bands 17q12 and 17q21 and at 15q22.

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